High concentration of topical amitriptyline for treating chemotherapy-induced neuropathies

Support Care Cancer. 2019 Aug;27(8):3053-3059. doi: 10.1007/s00520-018-4618-y. Epub 2019 Jan 4.


Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is a devastating pain condition of cancer therapy that may force chemotherapy dose reduction or discontinuation. Since treatment options for CIPN are quite limited, we investigated the effect of 10% amitriptyline cream on neuropathic pain.

Patients and methods: This pilot study enrolled patients with hematological or solid tumors presenting hands and feet CIPN (for less than 1 month without previous treatment for CIPN [Group 1]; for more than 1 month with previous treatment [Group 2]). Patients applied 10% amitriptyline cream twice a day. Pain intensity was evaluated at 1, 2, and 4 weeks then monthly up to 1 year. The primary endpoint was change from baseline to 4-week treatment in median pain score assessed by visual analogue scale (VAS).

Results: Overall, 44 patients were enrolled. Median (range) age was 67 (46-80) years, 34% were female. The majority (88.6%) had hematological malignancies, and the most commonly used chemotherapeutic agents were bortezomib and oxaliplatin. The median (range) VAS pain score decreased from 7 (4-9) at baseline to 2 (0-4) after 4-week topical treatment. No difference was seen between Group 1 and Group 2. Reduced initial chemotherapy doses in 11 patients as well as chemotherapy discontinued in 5 patients at baseline were resumed after treatment with 10% amitriptyline cream.

Conclusion: Considering the limited efficacy of conventional systemic treatments in CIPN and their safety profile, 10% topical amitriptyline appears to be a good candidate for first-line CIPN therapy, allowing continuation of chemotherapy at effective doses. The results are worth to be confirmed in a placebo-controlled clinical trial.

Keywords: Amitriptyline cream; CIPN; Neuropathy; Pain; Supportive care.

Publication types

  • Clinical Trial

MeSH terms

  • Administration, Cutaneous
  • Administration, Topical
  • Aged
  • Aged, 80 and over
  • Amitriptyline / administration & dosage*
  • Analgesics, Non-Narcotic / administration & dosage
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Bortezomib / administration & dosage
  • Bortezomib / adverse effects
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / drug therapy
  • Neuralgia / chemically induced*
  • Neuralgia / drug therapy*
  • Oxaliplatin / administration & dosage
  • Oxaliplatin / adverse effects
  • Peripheral Nervous System Diseases / chemically induced*
  • Peripheral Nervous System Diseases / drug therapy*
  • Pilot Projects


  • Analgesics, Non-Narcotic
  • Antineoplastic Agents
  • Oxaliplatin
  • Amitriptyline
  • Bortezomib